The proposed research has been designed to investigate the questions, of DNA replication, DNA repair, and recombination pathways in the higher eucaryote, Drosophila melanogaster. These investigations will involve genetic, biochemical and cytological experiments and have been patterned after studies on recombination proficiency in procaryotic systems. Genetic studies will be aimed at isolating mutagen-sensitive and mutagen-resistat strains in order to recover strains defective in recombination proficiency and preliminary pilot experiments have suceeded in isolating a mutagen-sensitive strain. Procaryotic systems predict that this type of mutant strain may be defective in essential enzymes involved in recombination and DNA repair mechanisms. The preliminary characterization of this mutant strain suggests that mutagen-sensitivity is a feasible methodology for isolating the mutant strains which will form the basis of biochemical and cytological investigations of the phenomena in question. Biochemial investigations will be concerned with the analysis of the enzyme activities which play a role in recombination, replication and repair. These investigations will have a two fold nature: (1) characterization on enzyme activities in wild type strains; and (2) comparison of these selected enzyme activities between wild type and mutant strains in order to understand their appropriate in vivo functions. Cytological experiments will take advantage of the unique chromosomal material of this dipteran, the polytene salivary gland chromosomes. Autoradiographic studies will be concerned with (1) replication comparisons between wild type and selected mutant strains; and, (2) the demonstration of DNA repair in wild type strains and comparisons of repair between wild type and selected mutagen-sensitive strains. Such basic studies should provide model guidelines for investigation of derangements of these phenomena, as has occurred, for example, with the UV light-induced human skin cancer, Xeroderma pigmentosum, essentially "DNA repair disease".